This application represents a small step in initiating studies to better understand the shared and divergent neurologic underpinnings of Fragile X Syndrome (FXS) and Autism Spectrum Disorder (ASD) as well as to expand our knowledge about the psychophysiology of these disorders. Although there is great variability in symptom severity and intellectual functioning among individuals diagnosed with FXS and ASD, affected individuals have difficulties in social interaction such as use of eye contact, social anxiety and social deficits, sensory hypersensitivity, poor motor coordination, and delayed speech development and echolalia. The prevalence of autism in individuals with Fragile X reported at 18- 33% (e.g., [1-6]); conversely, the prevalence of FXS in individuals with ASD has been reported as approximately 2-8% [7, 8]. Shared attention deficits are one of the most consistent early predictors of social and language deficits in autism (e.g., [9]). In FXS, one of the most noted behaviors is eye gaze avoidance due to hyperarousal or aversiveness ([10]). While both groups demonstrate impairments or alterations in the use of eye gaze, it is unclear if these behaviors share the same underlying neural mechanisms. This project has three goals: (1) to investigate whether alterations in neural responses measured using event-related potentials underlie the behavioral phenotype of abnormal attention to and use of eye gaze in individuals with ASD and FXS. (2) To examine if individuals with FXS and ASD are able to use eye gaze cues to facilitate behavior in a task with low social demand. (3) To determine whether speed of neural response to faces is related to behavioral use of eye gaze in an exploratory task that has high social demand. To date, no studies have concurrently examined these abilities in matched groups of individuals with FXS and ASD. Furthermore, the ERP measures proposed in this project can be used across the lifespan as well as with individuals with limited cognitive skills allowing similar measures to be used across the phenotype of both disorders. Long term objectives include investigation of the relation of eye gaze behaviors to the development of social deficits, identification of links between ERP responses to social stimuli and the behavioral phenotype and biological markers of FXS and ASD, and use of ERPs to understand the etiology of social deficits in FXS and ASD, to help predict outcome, and to chart developmental progress. This application is a pilot study that will demonstrate the feasibility of utilizing electrophysiological measures to characterize Fragile X Syndrome (FXS) and Autism Spectrum Disorder (ASD) by focusing on a common area of behavioral impairment - eye gaze processing. This project directly addresses the goals of: (1) characterizing and understanding of pathophysiological mechanisms common to both FXS and ASD; (2) understanding neural pathways, circuits, and systems that play a role in the etiology or pathophysiology of FXS and may be implicated in autism; (3) studies providing detailed characterization of phenotypic and endophenotypic similarities and distinctions in the course of the two disorders; and (4) electrophysiological studies to identify specific abnormalities in patients with FXS and ASD. [unreadable] [unreadable] [unreadable] [unreadable]